Protein-tyrosine phosphatase 1B substrates and metabolic regulation

Jesse Bakke, Fawaz G. Haj

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations


Metabolic homeostasis requires integration of complex signaling networks which, when deregulated, contribute to metabolic syndrome and related disorders. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as a key regulator of signaling networks that are implicated in metabolic diseases such as obesity and type 2 diabetes. In this review, we examine mechanisms that regulate PTP1B-substrate interaction, enzymatic activity and experimental approaches to identify PTP1B substrates. We then highlight findings that implicate PTP1B in metabolic regulation. In particular, insulin and leptin signaling are discussed as well as recently identified PTP1B substrates that are involved in endoplasmic reticulum stress response, cell-cell communication, energy balance and vesicle trafficking. In summary, PTP1B exhibits exquisite substrate specificity and is an outstanding pharmaceutical target for obesity and type 2 diabetes.

Original languageEnglish
Pages (from-to)58-65
Number of pages8
JournalSeminars in Cell and Developmental Biology
StatePublished - Jan 1 2015


  • Diabetes
  • ER stress
  • Obesity
  • PTP1B
  • Pyruvate kinase
  • Substrate


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